Evaluation of the Effect of Induced Endotoxemia on ROTEM S® and Platelet Parameters in Beagle Dogs Anaesthetized with Sevoflurane.

Endotoxemia is thought to induce severe changes in coagulation status. In this study, blood samples from six beagle dogs receiving 1 mg/kg E. coli lipopolysaccharide (LPS) intravenously were analyzed to describe the concurrent changes in platelet count, platelet function assessed with impedance thromboaggregometry, thromboelastometry and d-dimers during artificially induced endotoxemia and its therapy with fluids and vasopressors at five timepoints (baseline, after LPS and 30 mL/kg Ringer's acetate, during noradrenaline ± dexmedetomidine infusion, after a second fluid bolus and a second time after vasopressors). Results were analyzed for changes over time with the Friedman test, and statistical significance was set at p < 0.05. We found decreased platelet count and function and changes in all platelet-associated rotational thromboelastometry (ROTEM) variables indicating hypocoagulability, as well as increases in d-dimers indicating fibrinolysis within one hour of intravenous administration of LPS, with partial recovery of values after treatment and over time. The fast changes in platelet count, platelet function and ROTEM variables reflect the large impact of endotoxemia on the coagulation system and support repeated evaluation during the progress of endotoxemic diseases. The partial recovery of the variables after initiation of fluid and vasopressor therapy may reflect the positive impact of the currently suggested therapeutic interventions during septic shock in dogs.

The impact of vatinoxan on microcirculation after intramuscular co-administration with medetomidine in Beagle dogs: a blinded crossover study.

OBJECTIVE: To measure the effects on microcirculation of medetomidine alone (MED) or combined with vatinoxan (MVX). STUDY DESIGN: Randomized, crossover, blinded, experimental study. ANIMALS: A group of eight healthy purpose-bred Beagle dogs. METHODS: Each dog was given 1 mg m-2 MED intramuscularly (IM) or combined with 20 mg m-2 vatinoxan IM (MVX) with a washout period of 7 days. A sidestream dark field (SDF) camera was placed on the buccal mucosa to assess the oral mucosal microcirculation for perfused DeBacker density, proportion of perfused vessels (PPV) (both for all vessels and vessels with a diameter < 20 µm), microvascular flow index (MFI) and heterogeneity index (HI). Videos were recorded at baseline (-5) and 10, 20, 30, 40, 60, 90 and 120 minutes after treatment administration. Linear mixed-effects models were used to assess if microvascular variables were significantly associated with treatment, baseline, and sequence. Results are presented as estimated effect (95% confidence interval), and a p value < 0.05 was considered significant. RESULTS: The interquartile range for baseline measurements was 91.49%-98.42% for PPV, 2.75-3 for MFI and 0-0.36 for HI. Significant effects of treatment and baseline were found. The estimated effect of MED against MVX was -1.98% (-3.53% to -0.42%) for PPV, -0.33 (-0.43 to -0.22) for MFI and 0.14 (0.05 to 0.22) for HI. There were no significant changes seen for perfused DeBacker density, perfused DeBacker density < 20 µm and PPV < 20 µm between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that MVX had significantly fewer effects on buccal mucosal microcirculation than MED. The SDF camera is a useful research tool to assess the microcirculatory status of heavily sedated dogs.

Evaluation of the ability of haemodynamic variables obtained with minimally invasive techniques to assess fluid responsiveness in endotoxaemic Beagles.

OBJECTIVE: To examine the ability of different haemodynamic variables recorded by minimally invasive monitoring techniques to assess fluid responsiveness (FR) in endotoxaemic Beagles. STUDY DESIGN: Prospective terminal experimental study. ANIMALS: A group of six healthy, purpose-bred Beagle dogs (three intact females and males), age 5-9.8 years (range) and weighing 11.4-17.9 kg. METHODS: Endotoxaemic shock was induced by injecting 1 mg kg-1Escherichia coli lipopolysaccharide (LPS) intravenously in six sevoflurane-anaesthetized mechanically ventilated Beagles for another project. After 10 minutes, three Ringer's acetate boluses (10 mL kg-1) were administered each over 10 minutes with collection of haemodynamic data immediately before and after each bolus. Thereafter, arterial hypotension was treated with noradrenaline ± dexmedetomidine until arterial pressures increased to a target value. After a wash-out period of 20 minutes another three boluses of fluid were administered and measurements were repeated equally. For each fluid bolus, FR was considered positive when change (Δ) in stroke volume measured by pulmonary artery thermodilution was ≥15%. To test predictive accuracy for FR, we recorded heart rate, invasive arterial, right atrial and pulmonary capillary wedge pressures, pulse wave transit time with haemodynamic monitors, calculated pulse pressure, shock index and rate over pressure evaluation (ROPE) and measured stroke distance and corrected flow time (FTc) with oesophageal Doppler monitoring. RESULTS: A total of 35 measurements (19 positive and 16 negative responses) were evaluated. A FTc < 330 ms, Δ pulse pressure ≥20%, Δ shock index ≤-14% and ΔROPE ≤-17% were the most significant indicators of positive FR with an area under the receiver operating characteristics curve between 0.72 and 0.74. CONCLUSIONS AND CLINICAL RELEVANCE: In endotoxaemic Beagles, none of the assessed haemodynamic variables could predict FR with high sensitivity and specificity.

Quantification of cerebrospinal fluid flow in dogs by cardiac-gated phase-contrast magnetic resonance imaging.

BACKGROUND: Cerebrospinal fluid (CSF) flow in disease has been investigated with two-dimensional (2D) phase-contrast magnetic resonance imaging (PC-MRI) in humans. Despite similar diseases occurring in dogs, PC-MRI is not routinely performed and CSF flow and its association with diseases is poorly understood. OBJECTIVES: To adapt 2D and four-dimensional (4D) PC-MRI to dogs and to apply them in a group of neurologically healthy dogs. ANIMALS: Six adult Beagle dogs of a research colony. METHODS: Prospective, experimental study. Sequences were first optimized on a phantom mimicking small CSF spaces and low velocity flow. Then, 4D PC-MRI and 2D PC-MRI at the level of the mesencephalic aqueduct, foramen magnum (FM), and cervical spine were performed. RESULTS: CSF displayed a bidirectional flow pattern on 2D PC-MRI at each location. Mean peak velocity (and range) in cm/s was 0.92 (0.51-2.08) within the mesencephalic aqueduct, 1.84 (0.89-2.73) and 1.17 (0.75-1.8) in the ventral and dorsal subarachnoid space (SAS) at the FM, and 2.03 (range 1.1-3.0) and 1.27 (range 0.96-1.82) within the ventral and dorsal SAS of the cervical spine. With 4D PC-MRI, flow velocities of >3 cm/s were visualized in the phantom, but no flow data were obtained in dogs. CONCLUSION: Peak flow velocities were measured with 2D PC-MRI at all 3 locations and slower velocities were recorded in healthy Beagle dogs compared to humans. These values serve as baseline for future applications. The current technical settings did not allow measurement of CSF flow in Beagle dogs by 4D PC-MRI.

Cardiovascular effects of two adenosine constant rate infusions in anaesthetized dogs.

OBJECTIVE: Adenosine induces vasodilatation. The aim of this study was to investigate cardiovascular effects of two adenosine constant rate infusion (CRI) doses in dogs. STUDY DESIGN: Experimental, longitudinal repeated measure design. ANIMALS: Ten healthy purpose-bred Beagle dogs. METHODS: Each dog was sedated with butorphanol. Anaesthesia was induced with propofol intravenously and maintained with sevoflurane (inspired oxygen fraction = 47-55%). Controlled mechanical ventilation was used to maintain normocapnia. Two doses of adenosine were administered as CRIs to each dog: 140 µg kg-1 minute-1 (A140) followed by 280 µg kg-1 minute-1 (A280). Pulse rate, invasive arterial pressure and stroke volume (by magnetic resonance phase contrast angiography) were measured at baseline, 3 minutes after starting adenosine and 3 and 10 minutes after discontinuing adenosine. Cardiac output, cardiac index and approximated systemic vascular resistances (approximate SVR) were calculated. Additionally, arterial blood gases, co-oximetry, electrolytes, glucose and lactate were measured and oxygen content and delivery calculated. One-way repeated measures analysis of variance (p < 0.05) was used for data analysis. RESULTS: A140 and A280 resulted in a significant decrease in arterial blood pressure [systolic (p = 0.008), mean (p = 0.003), and diastolic arterial pressure (p = 0.004)] and approximate SVR (p = 0.008) compared with baseline. No significant changes were detected for the other variables. All values returned to baseline within 3 minutes after adenosine discontinuation. CONCLUSIONS AND CLINICAL RELEVANCE: Adenosine CRI decreases arterial pressure by vasodilatation in healthy dogs. No additional effects were observed with the higher dose. The effects in compromised dogs remain to be investigated.

Assessment of Myocardial Perfusion at Rest and During Stress Using Dynamic First-Pass Contrast-Enhanced Magnetic Resonance Imaging in Healthy Dogs.

Objective: To assess the feasibility of myocardial perfusion analysis in healthy dogs using dynamic contrast-enhanced cardiac magnetic resonance (DCE-MR) imaging at rest and during simulated stress with two doses of adenosine. Animals: Ten healthy beagle dogs. Procedures: Dogs were anesthetized and positioned in dorsal recumbency in a 3.0 Tesla MR scanner. Electrocardiogram-triggered dynamic T1-weighted ultrafast gradient echo images of three slices in short-axis orientation of the heart were acquired during breath holds and the first pass of gadolinium contrast. Image acquisition was performed after 4 min infusion of 140 µg/kg/min and 280 µg/kg/min adenosine and, after a washout period, without adenosine, respectively. Images were processed by dividing each slice into 6 radial segments and perfusion analysis was performed from signal intensity-time data. Results: No differences in perfusion parameters were found between segments within any of the slices, but significant differences were found between slices for peak enhancement, accumulated enhancement, and the maximum upslope. In addition, significant differences were found within each slice between data at rest and during adenosine-induced stress for the relative and absolute maximum upslope, relative peak enhancement, time to peak, and accumulated enhancement although inter-individual variation was large and no difference was found between the two stress tests for some parameters. Conclusion and Clinical Relevance: Results of this study showed that rest and stress myocardial perfusion can be assessed using DCE-CMR in dogs using the methods described. Both, adenosine dose and slice appear to affect perfusion parameters in healthy dogs and individual response to adenosine was variable.

Comparison of three continuous positive airway pressure (CPAP) interfaces in healthy Beagle dogs during medetomidine-propofol constant rate infusions.

OBJECTIVE: To compare the efficacy of three continuous positive airway pressure (CPAP) interfaces in dogs on gas exchange, lung volumes, amount of leak during CPAP and rebreathing in case of equipment failure or disconnection. STUDY DESIGN: Randomized, prospective, crossover, experimental trial. ANIMALS: Ten purpose-bred Beagle dogs. METHODS: Dogs were in dorsal recumbency during medetomidine-propofol constant rate infusions, breathing room air. Three interfaces were tested in each dog in a consecutive random order: custom-made mask (M), conical face mask (FM) and helmet (H). End-expiratory lung impedance (EELI) measured by electrical impedance tomography was assessed with no interface (baseline), with the interface only (No-CPAP for 3 minutes) and at 15 minutes of 7 cmH2O CPAP (CPAP-delivery). PaO2 was assessed at No-CPAP and CPAP-delivery, partial pressure of inspired carbon dioxide (PICO2; rebreathing assessment) at No-CPAP and the interface leak (ΔPleak) at CPAP-delivery. Mixed-effects linear regression models were used for statistical analysis (p<0.05). RESULTS: During CPAP-delivery, all interfaces increased EELI by 7% (p<0.001). Higher ΔPleak was observed with M and H (9 cmH2O) in comparison with FM (1 cmH2O) (p<0.001). At No-CPAP, less rebreathing occurred with M (0.5 kPa, 4 mmHg) than with FM (1.8 kPa, 14 mmHg) and with H (1.4 kPa, 11 mmHg), but also lower PaO2 was measured with M (9.3 kPa, 70 mmHg) than with H (11.9 kPa, 90 mmHg) and FM (10.8 kPa, 81 mmHg). CONCLUSIONS AND CLINICAL RELEVANCE: All three interfaces can be used to provide adequate CPAP in dogs. The leak during CPAP-delivery and the risk of rebreathing and hypoxaemia, when CPAP is not maintained, can be significant. Therefore, animals should always be supervised during administration of CPAP with any of the three interfaces. The performance of the custom-made M was not superior to the other interfaces.